Y. lipolytica is a dimorphic, aerobic yeast generally considered non-pathogenic due to its low maximal growth temperature. In light of this, it has been classified by the Food and Drug Agency as generally regarded as safe. This organism is notable for its unusual metabolism—it can metabolise few sugars but is able to break down and use a number of hydrophobic substances, including long-chain fatty acids. The organism is easy to transform, with good transformation efficiency and stability being observed. In addition, development of recombinant promoters in this organism has allowed high levels of expression to be achieved in nearly all growth mediums (Nicaud et al (2002); FEMS Yeast Research; volume 2; pg 371-379).
The use of yeasts such as Y. lipolytica for expression of proteins is necessary due to the inability of bacterial expression systems to perform mammalian post-translational modification of proteins.
Yeasts, along with Eukaryotic cell cultures and genetically engineered plants, are able to perform some or all of these modifications and thus produce a superior product. Yeasts, especially, have a number of advantages when used in this manner: a well-understood culture methodology, purification regime, rapid biomass conversion and the ability to perform most mammalian post-translational modifications. This facility can also be improved using genetic engineering—for instance, the insertion of human genes catalysing glycosylation—for which yeasts are also admirably suited.
However, the most commonly used representative of the yeast family—Saccharomyces cerevisiae—has certain limitations, such as low heterologous protein production in culture and hyperglycosylation of recombinant proteins. The potential advantages of other yeast species as expression systems, including more mammalian-like post-translational modifications of proteins and the ability to use other carbon sources, has lead research into these organisms as alternatives to S. cerevisiae. Four of these species; Hansenula polymorphs, Pichia pastoris, Arxula adeninivorans and Yarrowia lipolytica; were reviewed in terms of their comparative advantages and disadvantages as expression systems (Gellisen et al (2005); FEMS Yeast Research; volume 5; pg 1079-1096). In this review, Y. lipolytica was identified alongside A. adeninivorans as having promising potential for industrial processes.
Accordingly, there is a need in the art for expression systems specific to Y. lipolytica for the production of polypeptides with biotechnological applications.